Summary of work: Progression of eukaryotic cells through the various phases of the cell cycle is controlled to a large extent by the cyclin-dependent kinase system. The critical catalytic activity of the kinases is regulated by a complex system involving coupling with a cyclin partner, phospho-rylation status of certain amino acid residues within the catalytic unit and also by a family of low molecular weight inhibitors. Among the cyclin-dependent kinases associated with the G1 phase, cyclin-dependent kinase 2 regulates the G1/S transition as wells as progression of the cells through the S phase. Two forms of cyclin-dependent kinase 2, alpha and beta, have been identified and shown to be a result of differential splicing. Both forms of this kinase complex with cyclin E, phosphorylate retinoblastoma protein and are inhibited by the cyclin-dependent kinase inhibitor p27Kip1. In murine T-cells, cyclin-dependent kinase 2 shows a differential kinase activity in that the beta form phosphorylates retinoblastoma protein to a greater extent than the alpha form at or near the G1/S transition while the alpha form is more active during early S phase. Although human genomic cyclin-dependent kinase 2 contains the information for both forms of the enzyme, the beta form of the enzyme is not detectable in various cell types. Various antimutagenic conditions or agents that arrest cells in the G1 of the cell cycle is associated with an increase in the level of p27Kip1 which results in the accumulation of enzymatically inactive cyclin/cyclin-dependent kinase 2 complexes. Ectopic over expression of p27Kip1 in the human cell line, HeLa, significantly reduced the colony forming capacity of the stably transfected cells. The colony forming capacity of Held cells transfected with p27Kip1 can be reinstated by ectopic expression of cyclin E in amounts that also restores the cdk2 associated kinase activity.